Energy metabolism in health and diseases

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Фев. 18, 2025

Язык: Английский

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Microglial regulation of white matter development and its disruption in autism spectrum disorder

Cerebral Cortex, Год журнала: 2025, Номер 35(4)

Опубликована: Апрель 1, 2025

Abstract White matter, comprising approximately 50% of the human brain, is crucial for efficient neuronal signaling and a wide range brain functions, including social cognition, sensation, memory, motor control, information integration across cortical regions in service perception cognition. composed myelinated axons, results from complex interactions between different cell types, with oligodendrocytes (OLs) microglia playing integral roles. Microglia, brain's resident immune cells, regulate oligodendrogenesis through phagocytosis molecular signaling, example cytokines, which promote inhibit maturation stages OL lineage cells. Maternal activation (MIA) recognized risk factor neurodevelopmental disorders, especially autism spectrum disorder (ASD). The physiological presentation ASD includes white matter abnormalities dysregulation. Emerging evidence indicates that MIA may reduce microglial reactivity alter cytokine release offspring, potentially disrupting delicate balance required proper development. Understanding intricate interplay oligodendrocytes, microglia, inflammation, development context provides valuable insights into etiology core symptoms possible therapeutic targets.

Язык: Английский

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Microglia, Trem2, and Neurodegeneration

The Neuroscientist, Год журнала: 2024, Номер unknown

Опубликована: Май 20, 2024

Microglia are a specialized type of neuroimmune cells that undergo morphological and molecular changes through multiple signaling pathways in response to pathological protein aggregates, neuronal death, tissue injury, or infections. express Trem2, which serves as receptor for multitude ligands enhancing their phagocytic activity. Trem2 has emerged critical modulator microglial activity, especially many neurodegenerative disorders. Human TREM2 mutations associated with an increased risk developing Alzheimer disease (AD) other diseases. plays dual roles neuroinflammation more specifically disease-associated microglia. Most recent developments on the mechanisms emphasizing its role uptake clearance amyloid β (Aβ) aggregates debris help protect preserve brain, encouraging. Although normally stimulates defense mechanisms, dysregulation can intensify inflammation, poses major therapeutic challenges. Recent approaches targeting via agonistic antibodies gene therapy methodologies present possible avenues reducing burden This review highlights promise target, Aβ-associated AD, calls mechanistic investigations understand context-specific effective therapies against

Язык: Английский

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Microglia and TREM2

Neuropharmacology, Год журнала: 2024, Номер 257, С. 110020 - 110020

Опубликована: Май 29, 2024

Язык: Английский

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Microglial polarization in Alzheimer's disease: Mechanisms, implications, and therapeutic opportunities

Journal of Alzheimer s Disease, Год журнала: 2025, Номер unknown

Опубликована: Фев. 2, 2025

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-β plaques, neurofibrillary tangles, and chronic neuroinflammation. Microglial cells, resident immune cells in central nervous system, play crucial role pathogenesis AD. Microglia can undergo polarization, shifting between pro-inflammatory (M1) anti-inflammatory (M2) phenotypes response to different stimuli. Dysregulation microglial polarization towards phenotype leads release inflammatory cytokines, oxidative stress, synaptic dysfunction. These processes contribute neuronal damage cognitive decline However, several challenges remain this field. The complex molecular mechanisms governing AD need be further elucidated. In review, we discuss underlying its implications progression.

Язык: Английский

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Microglia in ALS: Insights into Mechanisms and Therapeutic Potential

Cells, Год журнала: 2025, Номер 14(6), С. 421 - 421

Опубликована: Март 12, 2025

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of motor neurons, leading to escalating muscle weakness, atrophy, and eventually paralysis. While neurons are most visibly affected, emerging data highlight microglia—the brain’s resident immune cells—as key contributors onset progression. Rather than existing in simple beneficial or harmful duality, microglia can adopt multiple functional states shaped internal external factors, including those ALS. Collectively, these disease-specific forms called disease-associated (DAM). Research using rodent models, patient-derived cells, human postmortem tissue shows that transition into DAM phenotypes, driving inflammation neuronal injury. However, cells also fulfill protective roles under certain conditions, revealing their adaptable nature. This review explores recent discoveries regarding multifaceted behavior ALS, highlights important findings link neuron deterioration, discusses therapies—some already used clinical trials—that aim recalibrate microglial functions potentially slow

Язык: Английский

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Immune cell metabolic dysfunction in Parkinson’s disease

Molecular Neurodegeneration, Год журнала: 2025, Номер 20(1)

Опубликована: Март 24, 2025

Abstract Parkinson’s disease (PD) is a multi-system disorder characterized histopathologically by degeneration of dopaminergic neurons in the substantia nigra pars compacta . While etiology PD remains multifactorial and complex, growing evidence suggests that cellular metabolic dysfunction critical driver neuronal death. Defects metabolism related to energy production, oxidative stress, organelle health, protein homeostasis have been reported both immune cells PD. We propose these factors act synergistically drive aberrant inflammation CNS periphery PD, contributing hostile inflammatory environment which renders certain subsets vulnerable degeneration. This review highlights overlap between established deficits with emerging findings central peripheral cells. By discussing rapidly expanding literature on immunometabolic we aim draw attention potential biomarkers facilitate future development immunomodulatory strategies prevent or delay progression

Язык: Английский

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Role of the prefrontal cortical protease TACE/ADAM17 in neurobehavioral responses to chronic stress during adolescence

Brain and Behavior, Год журнала: 2024, Номер 14(5)

Опубликована: Май 1, 2024

Abstract Introduction Chronic adolescent stress profoundly affects prefrontal cortical networks regulating top‐down behavior control. However, the neurobiological pathways contributing to stress‐induced alterations in brain and remain largely unknown. influences growth factors immune responses, which may, turn, disrupt maturation function of networks. The tumor necrosis factor alpha‐converting enzyme/a disintegrin metalloproteinase 17 (TACE/ADAM17) is a sheddase with essential functions maturation, behavior, inflammatory responses. This study aimed determine impact on cortex whether TACE/ADAM17 plays role these Methods We used Lewis rat model that incorporates critical elements chronic psychosocial stress, such as uncontrollability, unpredictability, lack social support, re‐experiencing trauma. Results during adolescence reduced acoustic startle reflex interactions while increasing extracellular free water content mRNA levels medial cortex. altered various ethological behavioral domains observation home cages (decreased ingestive behaviors increased walking, grooming, rearing behaviors). A group rats was injected intracerebrally either novel Accell™ SMARTpool siRNA or corresponding vehicle (control). RNAscope Multiplex Fluorescent v2 Assay visualize expression. Automated puncta quantification analyses demonstrated administration (59% reduction relative control). found received exhibited eating patterns (e.g., food intake time feeding zone light cycle). Conclusion supports sensitive suggests may be involved responses stress.

Язык: Английский

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Glial polarization in neurological diseases: Molecular mechanisms and therapeutic opportunities

Ageing Research Reviews, Год журнала: 2024, Номер 104, С. 102638 - 102638

Опубликована: Дек. 12, 2024

Язык: Английский

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The role of microglial TREM2 in development: A path toward neurodegeneration?

Glia, Год журнала: 2024, Номер 72(9), С. 1544 - 1554

Опубликована: Июнь 5, 2024

Abstract The nervous and the immune systems undergo a continuous cross talk, starting from early development continuing throughout adulthood aging. Defects in this talk contribute to neurodevelopmental neurodegenerative diseases. Microglia are resident cells brain that primarily involved bidirectional communication. Among microglial genes, trem2 is key player, controlling functional state of microglia being at forefront many processes require interaction between other components, such as neurons oligodendrocytes. present review focuses on developmental window, describing which TREM2 involved, including modulation synapse formation elimination, control neuronal bioenergetic states well contribution myelination circuit formation. By causing imbalances during these maturation phases, dysfunctional may have striking impact adult brain, making it more sensitive target for insults occurring

Язык: Английский

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